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Nccu journal club 2.5.13


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Nccu journal club 2.5.13

  1. 1. NCCU Journal Club JOSHUA KORNBLUTH, MD F E B 5 TH, 2 0 1 3
  2. 2.  Objective: to review a recent randomized trial of intracranial pressure monitoring in sTBI To encourage thought and discussion of our own practices To consider future directions Nothing for me to disclose
  3. 3. Study Overview Does intracranial pressure monitoring improve outcomes in severe TBI? What is the current standard of care in America? Why does this question matter? Multicenter, 324 adult pts, severe TBI, randomized to two separate protocols Looked at in-hospital events, survival time and 3- and 6- month outcomes
  4. 4. You heard it from the BTF…
  5. 5. Study Overview Can we conduct this type of study in America? Highly unlikely, so lets take advantage of alternative standards of care to investigate. Study Design  Multicenter, parallel-group trial  Random assignment to ICP-monitoring group vs imaging- clinical examination group  Study started in Bolivian hospitals, and additional hospitals were added later to increase enrollment
  6. 6. Study Design – Inclusion Criteria Traumatic brain injury GCS < 8 on admission or within first 48 hours after injury (Motor score ≤ 5 if intubated) Admission to study hospital within 24 hours of injury No foreign object in the brain parenchyma. Age > 12 Randomized:  within 24 hours of injury [for patients with GCS < 8 on admission] or  within 24 hours of deterioration [patients deteriorating to GCS < 8 within 48 hours of injury Randomization stratified according to site, injury severity score, and age
  7. 7. Study Design – Exclusion Criteria GCS of 3 with bilateral fixed and dilated pupils No consent Pregnant Prisoner No beds available in ICU No ICP monitor available Non-survivable injury Other (e.g., Pre-injury life expectancy under 1 year) Pre-existing neurological disability that would confound outcome
  8. 8. Study Design - protocol Place patient on mechanical ventilation (VM) Place continuous SaPO2 and EtCO2 monitors Insert indwelling urinary catheter to monitor urine output Insert arterial catheter for arterial mean pressure monitoring Insert central venous catheter for infusion of solutions and central venous pressure monitoring. Monitor neurological clinical status each hour  Pupils  GCS Brain CT  To evaluate evolution 48 hours after the admission CT  To evaluate evolution 5-7 days after the admission CT  p.r.n.
  9. 9. Study Design – Standards of Critical Care Clearly delineate standard basic Critical Care• Head positioning 30º• Head and neck in neutral position and aligned• Avoid hyperthermia (Defined as central temperature > 38 º C) • Non-drug measures (cooling) • Dipirona (Metamizole sodium)• Early enteral nutritional support • Before 48 hours • 25 Kcal/kg weight• Pharmacologic prophylactic of post traumatic seizures (Phenytoin (IV or PO)) • Load and maintenance dose as is being giving in each hospital• Gastric bleeding prophylaxis • Ranitidine or Omeprazol• Avoid decubitus lesions• Deep venous thrombosis prophylaxis• Frequent tracheal suctioning with sterile technique to prevent pulmonary infections
  10. 10. Study Design – ICP group Had parenchymal monitor ASAP (i.e. after randomization and resolution of coagulopathy if present) Position was not specified Treat if ICP≥20mmHg x 5min If CSF drainage indicated, EVD placed CPP goal 50-70mmHg
  11. 11. Study Design – Treatments (ICP Group) Treatments based on a “Therapeutic Intensity Level” If signs of intracranial HTN, clinical or imaging  1 – hyperosmolar therapy (mannitol)  5% NaCl only if hypotenisve, hypovolemic, hyponatremic  2 – optional mild hyperventilation (pCO2 30-35mmHg)  3 – Ventricular drainage if possible*
  12. 12. Study Design – Definitions (ICP Group) Intracranial Pressure Definitions:  Treatable intracranial hypertension:  ICP > 20 mmHg for > 5 minutes  Treatment failure:  ICP not reduced to ≤ 20 mmHg within 20 minutes after a treatment intervention is initiated, and  Persistent elevation in ICP > 20 mmHg requires increase in therapeutic intensity level
  13. 13. Study Design – “Neuroworsening” Neuroworsening = Inc’d TIL  1. Decrease in the motor GCS > 2  2. New loss of pupil reactivity  3. Interval development of pupil asymmetry of > 2mm  4. New focal motor deficit  5. Herniation syndrome Give mannitol 0.25-1mg/kg to sOSM<320 Hyperventilate to pCO2 25-30 If no response  thiopental x 3d Craniectomy for space-occupying lesions
  14. 14. Study Design – Imaging only Group After optimized sedation and analgesia, hyperventilation and hyperosmotic therapy should be started simultaneously if there is evidence of edema on CT, as indicated as following:  1. Compressed peri-mesencephalic cisterns  2. Midline shift  3. Cortical sulcal compression / effacement Otherwise, same metrics and goals of ICP monitored group Corticosteriods prohibited AED’s for prophylaxis >28d
  15. 15. Study Design - Outcomes Primary outcome – 21-point composite of survival, duration and level of impaired consciousness, 3- month GOSe and GOAT, 6-month GOSe and neuropsych testing Secondary Outcomes – ICU LOS, number of days that patients received at least 1 brain-specific treatment, days of MV, treatment with high-dose barbiturates, decompressive crani
  16. 16. Results
  17. 17. Results - Demographics
  18. 18. Results MVA’s accounted for most injuries (51% of randomized pts) 45% of pts were brought in by ambulance Remainder were transferred from other facilities Did not publish pre-hospital demographics or interventions as these we not uniformly recorded
  19. 19. Results - Demographics 24% of randomized patients had clinical decline to GCS within eligibility criteria 49% of patients had localizing signs on clinical exam 33% of participants required surgical treatment of mass lesions On initial CT, 85% had cisternal compression and 36% had >5mm midline shift
  20. 20. Results – Clinical Outomes
  21. 21. HR for death at 6mos =1.10,slightly in favor of ICP group
  22. 22. Results – Subgroup Analysis Hospital LOS was slightly shorter in the ICE group (iqr 12 for ICP, 9 for ICE) No significant differences in MV days, of non-neurologic complications  Except ICP-monitored pts had a higher incidence of decubitus ulcers (12%vs 5%, P=0.03) Median time of ICP monitoring was 3.6d Incidence of Neuroworsening after randomization was 25% in the entire study, and was similar in both groups Median interval for brain-specific treatments was longer in ICE group Use of barbiturates was significantly higher in the ICP group (24% vs 13%) HTS and HV were used more in the ICE group (72% vs 58%, 73% vs 60%)
  23. 23. Results Almost every variable, including LOS, mortality, anf functional outcomes favored ICP monitoring with a HR>1. The study was powered to detect statistical significance of HR>1.5 Subgroup analysis of HR accounting for Marshall CT Classification
  24. 24. Results Summary Composite endpoints between the two groups were similar (P=0.49)  ICP group = 56  ICE group = 53 Mortality at 6 months (P=0.06)  ICP group=39%  ICE group=41% ICE group had more days of brain specific treatments (hyperosmolar therapy, HV)
  25. 25. Discussion So what did the trial show? Clinicians act on ICP, without clinical correlate as evidenced by the increased use of barbiturates Clinicians also act on clinical findings without quantitative evidence of intracranial hypertension as evidenced by more brain-specific treatments overall in the ICE group. Is this because increased ICP could herald clinical changes and early interventions abort herniation events? Also, radiographic signs may not translate to the parenchymal monitor.
  26. 26. Discussion - Skepticism South America – differences in pre-hospital, and post- hospital care Less might survive to hospital or to hospital transfer Rehabilitation standards are different and may not translate to the same cognitive recovery 35%death in all groups after 14d Adjusted estimates of sTBI mortality in the US varies from 41%-25% (J Neurotrauma. 2012 Jan 1;29(1):47-52., J Neurotrauma. 2012 Jan 1;29(1):47-52.) The “Thereapeutic Intensity Level” is a good overall metric but others such as %responders to ICP-lowering therapy has proven predictive and should have been incorporated (J Neurosurg. 2011 May;114(5):1471-8)
  27. 27. Discussion - Skepticism Technology – parenchymal monitors as standard Triggers for treatment? – ICP>20 x 5 min vs radiographic signs with or without clinical correlates ICP group – ICP triggers  ICP is too simplistic a reflection of intracranial pathophysiology. No account for CPP Clinical signs don’t always reflect global pressures and vice versa No discussion of inclusion/exclusion of polytrauma and surgical interventions
  28. 28. Discussion - Skepticism Variability in treatments (i.e. more mannitol and HV in the ICE group) may be because the ICE group had scheduled scans and interventions and the ICP group had more event-related treatment triggers Conversely, that may explain why the ICP group had more barbiturates and HTS
  29. 29. Discussion - benefits Very rigorous treatment algorithm for management of elevated ICP (either qualitative or quantitative) Homogenous population across countries Both groups had intracranial HTN treated… that isn’t in question In truth, this study did not test ICP monitoring, only a very specific treatment algorithm to an ICP threshold compared with clinical exam In the end, the neurologic exam might STILL be the best tool in our disposal.
  30. 30. Further Discussion This was probably the only way that this type of trial could be done Authors were careful not to compare South American patients to our own, only report their findings The goal of therapies was to lower the average ICP within the head – this doesn’t accurately reflect mechanical compression and injury to diepnephalic which may portend a worse prognosis. The clinical signs of elevated ICP (pupil dilations, posturing, coma) are directly related to these areas.
  31. 31. Further Discussion How would you alter the study? Could multimodal monitoring be the next step? Are composite endpoints more useful that single variable? i.e. mortality? Return to work? Is a 6-month outcome long enough? Don’t forget that even the most rigorous study cannot account for all possible variables and that this data might not apply to every patient.